Subthreshold Laser Treatment in Intermediate Age-related Macular Degeneration With Nascent Geographic Atrophy Study (LIANA)
Primary Purpose
Age-Related Macular Degeneration
Status
Recruiting
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
2RT subthreshold nanosecond laser
Sponsored by
About this trial
This is an interventional treatment trial for Age-Related Macular Degeneration focused on measuring Laser, Subthreshold nanosecond laser, Nascent geographic atrophy
Eligibility Criteria
Inclusion Criteria:
- Age 50 years or older at time of consent
- Best corrected visual acuity (BCVA) of 59 letters (Snellen equivalent of 6/19) or better in both eyes
- Bilateral large (>125µm) drusen as seen on colour fundus photographs (CFP) as assessed within a circle with radius of 3000µm centred on the fovea
- Between 1 to 5 (inclusive) discrete area/s of nascent geographic atrophy (nGA) as seen on SD-OCT B-scan/s within a 20°x20° volume scan centred on the fovea in the study eye NOTE: The non-study eye may have no nGA or any number of nGA lesions but not cRORA (on B-scan) or GA (on CFP).
- Ability, willingness and sufficient cognitive awareness to consent to the trial, received randomized SNL treatment or sham procedure, and complete all visits as per the study schedule
Exclusion Criteria:
- A cluster of definitely present reticular pseudodrusen (RPD) of >1 disc area (DA) as seen on infrared (IR) imaging, or fundus autofluorescence (FAF) within a 20°x20° field centred on the fovea
- Any evidence of definite geographic atrophy (GA)
- Any evidence of OCT-atrophy greater than nGA i.e. complete RPE and outer retinal atrophy (cRORA) as determined on a SD-OCT 20°x20° volume scan centred on the fovea
- Any evidence of active, regressed or treated macular neovascularization (MNV), in either eye, or active peripapillary CNV in the study eye (determined on multi-modal imaging and a fundus fluorescein angiogram is only required if in the investigator's medical judgement) NB: Subretinal fluid (SRF) <100µm or SRF associated with a subfoveal pseudovitelliform lesion permitted (i.e. slither/draping/ vitelliform with no evidence of new vessels on OCT-A) is not considered MNV and can be enrolled.
- A subfoveal pigment epithelial detachment (PED)/drusenoid detachment >1000µm in diameter (measured on the central B-scan) with hyperreflective foci (HRF) and increased choroidal transmission or any PED >2000µm measured at the central foveal B-scan
- Any other investigational treatment for AMD, excluding dietary supplements, received in the past 12 months or thought, in the opinion of the investigator, likely to chronically change the course of the subject's retinal disease
- Current participation in any other investigational ophthalmological clinical trial
Any ocular disease in the study eye, other than AMD, which in the opinion of the investigator may significantly compromise assessment of the retina, or which would compromise the ability to assess any effect following SNL treatment including, but not limited to:
- Diabetic retinopathy (unless limited to fewer than 10 microaneurysms and/or small retinal hemorrhages, without retinal thickening on OCT)
- Macular pathology or pigmentary abnormalities atypical of AMD, including but not limited to: pattern dystrophy, myopic maculopathy, angioid streaks, resumed ocular histoplasmosis syndrome, central serous choroidopathy, visually-significant epiretinal membranes, macular hole or pseudohole
- Optic nerve pathology, including optic atrophy, history of optic neuropathy
- Myopic crescent wider than 50% of the longest diameter of the optic disc, or closer than 1500 µm to the fovea
- Retinal vascular diseases including branch or central vein or artery occlusion
- Choroidal nevus within 2 disc diameters (DD) of the fovea associated with depigmentation or overlying drusen, if these drusen are used to determine eligibility
- Active uveitis or ocular inflammation
- History or presence of uncontrolled glaucoma
- Intraocular pressure which would preclude safe dilation of the pupil to allow adequate assessment and application of SNL treatment
- History of prior laser surgery to the retina including subthreshold laser (focal retinopexy for a peripheral break and/or focal retinal tears performed more than 90 days prior to the entry into the study is permitted)
- Significant cataract or other ocular media which, in the opinion of the investigator, significantly limits the visual acuity or view of the retina
- Previous retinal or ocular surgery, the effects of which may now or in the future complicate assessment of the progression of AMD. (Cataract surgery is allowed as long as it was performed over 90 days prior to entry into the study)
- Known hypersensitivity to fluorescein
- Sensitivity to application of a contact lens
- Corneal pathology precluding visualization of fundus or increasing the risk of using a contact lens, such as corneal dystrophy, recurrent corneal erosion syndrome or sensitivity to the application of a contact lens.
- Use of any systemic or ocular medication known to be toxic to the retina, excluding tamoxifen unless there is evidence of toxicity.
- Pregnant or lactating women
- Subject who is considered ineligible for this study in the investigator's medical judgment
Sites / Locations
- Centre for Eye Research AustraliaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active laser
Sham laser
Arm Description
Application of the active 2RT sub threshold laser
Application of sham laser (i.e. flashing lights which replicate the look of active laser to the participant)
Outcomes
Primary Outcome Measures
Rate of progression to advanced AMD in study eyes
The time to develop advanced AMD - as defined as choroidal neovascularization (CNV), geographic atrophy (GA), or OCT-defined cRORA - in the SNL-treated compared to sham-treated study eyes over 12 months
Secondary Outcome Measures
Rate of retinal sensitivity change in study eyes
The rate of change in mean retinal sensitivity over time (in decibels per year) of the SNL-treated compared to sham-treated study eyes over 12 months.
Full Information
NCT ID
NCT05200624
First Posted
December 9, 2021
Last Updated
March 24, 2023
Sponsor
Center for Eye Research Australia
Collaborators
AlphaRET Pty Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05200624
Brief Title
Subthreshold Laser Treatment in Intermediate Age-related Macular Degeneration With Nascent Geographic Atrophy Study
Acronym
LIANA
Official Title
Subthreshold Laser Treatment in Intermediate Age-related Macular Degeneration With Nascent Geographic Atrophy Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Center for Eye Research Australia
Collaborators
AlphaRET Pty Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a prospective, single centre, randomized, sham-controlled, double-masked, clinical trial which aims to investigate the effect of subthreshold nanosecond laser on disease progression in eyes with intermediate age-related macular degeneration (AMD) and nascent geographic atrophy by functional and anatomical outcomes.
The study population will be individuals with high-risk intermediate age-related macular degeneration who meet all eligibility criteria. 60 subjects total (30 randomized to receive subthreshold nanosecond laser (SNL) treatment and 30 to receive sham treatment as per the 1:1 randomization).
The study has a 12-month study period with four scheduled visits: screening, randomisation (first treatment), 6-month follow up visit (with second treatment where eligible), 12-month follow-up.
The primary outcome is the proportion of laser-treated study eyes that develop late AMD compared to sham-treated study eyes over 12 months. The key secondary outcome is the change in retinal function of laser-treated study eyes compared to sham-treated study eyes over 12 months. Safety will be the proportion of laser-treated eyes that lose 10+ letters of vision (measured on a standard vision chart) compared to sham-treated eyes over 12 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Age-Related Macular Degeneration
Keywords
Laser, Subthreshold nanosecond laser, Nascent geographic atrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active laser
Arm Type
Active Comparator
Arm Description
Application of the active 2RT sub threshold laser
Arm Title
Sham laser
Arm Type
Sham Comparator
Arm Description
Application of sham laser (i.e. flashing lights which replicate the look of active laser to the participant)
Intervention Type
Device
Intervention Name(s)
2RT subthreshold nanosecond laser
Other Intervention Name(s)
2RT, SNL
Intervention Description
The 2RT™ Q-switched YAG laser (532nm) delivering 3 nanosecond pulses; 400 um spot size, is a pulsed subthreshold nanosecond (SNL) laser, which uses low energy levels to produce limited effects that selectively target melanosomes within the pigmented retinal pigment epithelial (RPE) cells.
Primary Outcome Measure Information:
Title
Rate of progression to advanced AMD in study eyes
Description
The time to develop advanced AMD - as defined as choroidal neovascularization (CNV), geographic atrophy (GA), or OCT-defined cRORA - in the SNL-treated compared to sham-treated study eyes over 12 months
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Rate of retinal sensitivity change in study eyes
Description
The rate of change in mean retinal sensitivity over time (in decibels per year) of the SNL-treated compared to sham-treated study eyes over 12 months.
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Safety Endpoint: Proportion of study eyes with a ≥10-letter loss in best-corrected visual acuity (BCVA)
Description
The proportion of eyes that lose ≥10 letters of BCVA in the SNL-treated compared to sham-treated study and fellow eyes over 12 months.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 50 years or older at time of consent
Best corrected visual acuity (BCVA) of 59 letters (Snellen equivalent of 6/19) or better in both eyes
Bilateral large (>125µm) drusen as seen on colour fundus photographs (CFP) as assessed within a circle with radius of 3000µm centred on the fovea
Between 1 to 5 (inclusive) discrete area/s of nascent geographic atrophy (nGA) as seen on SD-OCT B-scan/s within a 20°x20° volume scan centred on the fovea in the study eye NOTE: The non-study eye may have no nGA or any number of nGA lesions but not cRORA (on B-scan) or GA (on CFP).
Ability, willingness and sufficient cognitive awareness to consent to the trial, received randomized SNL treatment or sham procedure, and complete all visits as per the study schedule
Exclusion Criteria:
A cluster of definitely present reticular pseudodrusen (RPD) of >1 disc area (DA) as seen on infrared (IR) imaging, or fundus autofluorescence (FAF) within a 20°x20° field centred on the fovea
Any evidence of definite geographic atrophy (GA)
Any evidence of OCT-atrophy greater than nGA i.e. complete RPE and outer retinal atrophy (cRORA) as determined on a SD-OCT 20°x20° volume scan centred on the fovea
Any evidence of active, regressed or treated macular neovascularization (MNV), in either eye, or active peripapillary CNV in the study eye (determined on multi-modal imaging and a fundus fluorescein angiogram is only required if in the investigator's medical judgement) NB: Subretinal fluid (SRF) <100µm or SRF associated with a subfoveal pseudovitelliform lesion permitted (i.e. slither/draping/ vitelliform with no evidence of new vessels on OCT-A) is not considered MNV and can be enrolled.
A subfoveal pigment epithelial detachment (PED)/drusenoid detachment >1000µm in diameter (measured on the central B-scan) with hyperreflective foci (HRF) and increased choroidal transmission or any PED >2000µm measured at the central foveal B-scan
Any other investigational treatment for AMD, excluding dietary supplements, received in the past 12 months or thought, in the opinion of the investigator, likely to chronically change the course of the subject's retinal disease
Current participation in any other investigational ophthalmological clinical trial
Any ocular disease in the study eye, other than AMD, which in the opinion of the investigator may significantly compromise assessment of the retina, or which would compromise the ability to assess any effect following SNL treatment including, but not limited to:
Diabetic retinopathy (unless limited to fewer than 10 microaneurysms and/or small retinal hemorrhages, without retinal thickening on OCT)
Macular pathology or pigmentary abnormalities atypical of AMD, including but not limited to: pattern dystrophy, myopic maculopathy, angioid streaks, resumed ocular histoplasmosis syndrome, central serous choroidopathy, visually-significant epiretinal membranes, macular hole or pseudohole
Optic nerve pathology, including optic atrophy, history of optic neuropathy
Myopic crescent wider than 50% of the longest diameter of the optic disc, or closer than 1500 µm to the fovea
Retinal vascular diseases including branch or central vein or artery occlusion
Choroidal nevus within 2 disc diameters (DD) of the fovea associated with depigmentation or overlying drusen, if these drusen are used to determine eligibility
Active uveitis or ocular inflammation
History or presence of uncontrolled glaucoma
Intraocular pressure which would preclude safe dilation of the pupil to allow adequate assessment and application of SNL treatment
History of prior laser surgery to the retina including subthreshold laser (focal retinopexy for a peripheral break and/or focal retinal tears performed more than 90 days prior to the entry into the study is permitted)
Significant cataract or other ocular media which, in the opinion of the investigator, significantly limits the visual acuity or view of the retina
Previous retinal or ocular surgery, the effects of which may now or in the future complicate assessment of the progression of AMD. (Cataract surgery is allowed as long as it was performed over 90 days prior to entry into the study)
Known hypersensitivity to fluorescein
Sensitivity to application of a contact lens
Corneal pathology precluding visualization of fundus or increasing the risk of using a contact lens, such as corneal dystrophy, recurrent corneal erosion syndrome or sensitivity to the application of a contact lens.
Use of any systemic or ocular medication known to be toxic to the retina, excluding tamoxifen unless there is evidence of toxicity.
Pregnant or lactating women
Subject who is considered ineligible for this study in the investigator's medical judgment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carly Parfett
Phone
+61399298263
Email
cera-rgo@cera.org.au
First Name & Middle Initial & Last Name or Official Title & Degree
Rebecca Singleton
Phone
+61399298369
Email
cera-rgo@cera.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robyn H Guymer, MBBS FRANZCO
Organizational Affiliation
Centre for Eye Research Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Eye Research Australia
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carly Parfett
Phone
+61 3 9929 8263
Email
cera-rgo@cera.org.au
First Name & Middle Initial & Last Name & Degree
Robyn H Guymer
12. IPD Sharing Statement
Plan to Share IPD
No
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Subthreshold Laser Treatment in Intermediate Age-related Macular Degeneration With Nascent Geographic Atrophy Study
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